PiT1 belongs to the inorganic phosphate (Pi) transporter (PiT)3 family (Transport Classification Database (TCDB) Number 2.A.20) comprising conserved symporters throughout all kingdoms that use either sodium or proton gradients to transport Pi. In mammals, the PiT family is comprised of only two members, PiT1 (SLC20A1) and PiT2 (SLC20A2), which were initially identified as receptors for retroviruses and were subsequently found to possess electrogenic Na+-Pi symporter activity. Due to the requirement of large amounts of Pi in bone physiology, the regulation of PiT1 has been well documented in bone and cartilage in vitro models. In osteoblast-like cells, PiT1, but not PiT2, mRNA expression and Na+-Pi cotransport are regulated by various factors such as Pi, epinephrine, insulin-like growth factor 1 (IGF-1), and bone morphogenic protein 2 (BMP2). Importantly, PiT1, but not PiT2 is upregulated during osteoblast differentiation, consistent with a dedicated role of PiT1 in this process. Expression and activity of PiT1 in chondrogenic cells was found to be regulated by extracellular Pi concentration and transforming growth factor-β (TGF-β). Moreover, vascular calcification occurring in pathological situations such as hyperphosphatemia-induced calcifications of blood vessels and osteoarthritis, shares a number of similarities with osteogenesis and bone mineralization. Recent in vitro studies have suggested that PiT1 may be implicated in pathological vascular calcification. Particularly, inhibition of Pi uptake by PiT1 small hairpin RNA in cultured vascular smooth muscle cells (VSMCs) blocked the expression of Pi-induced osteogenic differentiation markers, Runx2 and osteopontin, indicating that PiT1 might be a major mechanism for controlling vascular calcification and VSMC phenotypic state.
However, it should be noted that the above-mentioned studies have been conducted in in vitro models and it is not clear which role PiT1 plays in normal bone or vascular physiology. Particularly, the discrete expression of PiT1 in a subset of hypertrophic chondrocytes late in development, its weak expression in osteoblasts and VSMCs together with its low transport capacity make it an unlikely candidate to face the tremendous Pi needs for bone or vascular calcification. Moreover, since most studies aimed at elucidating PiT1 regulation and function were conducted in tissues in which Pi per se plays an important role (i.e. mineralized tissues), very little information is available for other tissues. Since PiT1 is expressed in numerous non-mineralizing tissues, it is entirely possible that PiT1 possesses regulated tissue-specific roles going beyond a housekeeping Na+-Pi transport function.
Cancer is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). Cancer is a generic term for a large group of diseases that can affect any part of the body and is a leading cause of death worldwide. The disease accounted for 7.4 million deaths (or around 13% of all deaths worldwide) in 2004 and deaths from cancer worldwide are projected to continue rising, with an estimated 12 million deaths in 2030 according the World Health Organization. The main types of cancer leading to overall cancer mortality each year are lung cancer, stomach cancer, colorectal cancer, breast cancer and liver cancer.
Amongst liver cancer, the most frequent is hepatocellular carcinoma (HCC) (also named hepatoma). Liver cancer is a fairly rare form of cancer in the western world (1% of all cancers) but much more common in Africa and parts of Asia (10% to 50% of all cancers). Having certain diseases may lead to liver cancer. These include cirrhosis of the liver, chronic alcoholism, chronic hepatitis C and chronic hepatitis B. People at risk for developing liver cancer also include those who are obese or have diabetes. Liver cancer is much more prevalent in men and incidence increases with age. This cancer is rapidly fatal, usually within 6 months from gastrointestinal hemorrhage, hepatic failure or metastasis.
It should be noted that liver cancer is most curable if caught in the earliest stage of the disease. However, there are generally no symptoms in early stages of liver cancer. If there are symptoms, they can be very vague and include nausea, weight loss, and loss of appetite. Therefore, a diagnosis of liver cancer can be missed or delayed because there are generally no symptoms in early stages of the disease.
However, as discussed above most solid tumors, including liver cancer, can often be cured only if they are detected and treated at an early stage.
Thus, there is still an existing need to develop a method for diagnosing cancer, notably liver cancer and more particularly during early-stage of liver cancer development.
There is also an urgent need to develop a method for prevention or treating cancer in particular liver cancer such as hepatocellular carcinoma.